title: Resistance to Streptozotocin-Induced Autoimmune Diabetes in Absence of Complement C3: Myeloid-Derived Suppressor Cells Play a Role.
abstract: The contribution of complement to the development of autoimmune diabetes has been proposed recently. The underlying mechanisms, however, remain poorly understood. We hypothesize that myeloid-derived suppressor cells (MDSC), which act as regulators in autoimmunity, play a role in resistance to diabetes in absence of complement C3. Indeed, MDSC number was increased significantly in STZ-treated C3-/- mice. These cells highly expressed arginase I and inducible nitric oxide synthase (iNOS). Importantly, depletion of MDSC led to the occurrence of overt diabetes in C3-/- mice after STZ. Furthermore, C3-/- MDSC actively suppressed diabetogenic T cell proliferation and prevented/delayed the development of diabetes in arginase and/or iNOS-dependent manner. Both Tregs and transforming growth factor-β (TGF-β) are crucial for MDSC induction in STZ-treated C3-/- mice as depletion of Tregs or blocking TGF-β bioactivity dramatically decreased MDSC number. These findings indicate that MDSC are implicated in resistance to STZ-induced diabetes in the absence of complement C3, which may be helpful for understanding of mechanisms underlying preventive effects of complement deficiency on autoimmune diseases.
authors.affiliation: Department of Organ Transplantation, Shanghai ChangZheng Hospital, Second Military Medical University, Shanghai, P. R. China.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Gao
authors.forename: Huanhai
authors.initials: H
authors.lastname: Liu
authors.forename: Bin
authors.initials: B
authors.lastname: He
authors.forename: Zhiren
authors.initials: Z
authors.lastname: Fu
mesh_terms: D000818:Animals; D018920:Coculture Techniques; D003176:Complement C3 / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D015536:Down-Regulation; D018836:Inflammation Mediators / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D000072737:Myeloid-Derived Suppressor Cells / Q000276:immunology*; D013311:Streptozocin
chemical_list: D003176:Complement C3; D016207:Cytokines; D018836:Inflammation Mediators; D013311:Streptozocin